How I treat Philadelphia chromosome–like acute lymphoblastic leukemia in children, adolescents, and young adults
Bibliographic record
Abstract
ABSTRACT: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) represents a high-risk B-lineage ALL subtype characterized by adverse clinical features and poor relapse-free survival despite risk-adapted multiagent chemotherapy regimens. The advent of next-generation sequencing has unraveled the diversity of kinase-activating genetic drivers in Ph-like ALL that are potentially amenable to personalized molecularly-targeted therapies. Based upon robust preclinical data and promising case series of clinical activity of tyrosine kinase inhibitor (TKI)-based treatment in adults and children with relevant genetic Ph-like ALL subtypes, several clinical trials have investigated the efficacy of JAK- or ABL-directed TKIs in cytokine receptor-like factor 2 (CRLF2)/JAK pathway-mutant or ABL-class Ph-like ALL, respectively. The final results of these trials are pending, and standard-of-care therapeutic approaches for patients with Ph-like ALL have yet to be defined. In this How I Treat perspective, we review recent literature to guide current evidence-based treatment recommendations via illustrative clinical vignettes of children, adolescents, and young adults with newly diagnosed or relapsed/refractory Ph-like ALL, and we further highlight open and soon-to-open trials investigating immunotherapy and TKIs specifically for this high-risk patient population.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".